In many biologic systems, growth factor mediated communication between different cell types is known to be an important regulator of cell proliferation and differentiation. In the lung, interactions among alveolar macrophages, type II pneumocytes and interstitial fibroblasts are potentially important for lung growth and for repair of the lung after injury. There is some evidence that these lung cells both produce and respond to growth factors and thus, growth factors may mediate these potentially regulatory intercellular communications. SCOR Project 1 focuses on the hypothesis that important interactions among lung cell populations are mediated through the synthesis and secretion of specific growth factors or cytokines. The goal is to identify the key control mechanisms which are involved in these interactions and determine how they are regulated during lung growth and repair of alveolar epithelial damage. The experiments proposed involve the isolation and culture of cells hypothesized to produce specific mediators, i.e., type II cells and macrophages, and taking media or purified fractions and evaluating their effects on the proposed target cells, the type II cell and the fibroblast. The studies described examine the ability of the alveolar macrophage and the type II cell, after activation either in vitro or by in vivo hyperoxic lung injury, to secrete known and novel growth factors. The synthesis and secretion of these molecules will be examined at the protein level, including characterization of the specific molecular forms produced, and at the level of expression of growth factor genes. Because cellular responses to growth factors may be altered during lung injury, the effects of growth factors on populations of cells isolated from normal and hyperoxia injured lung will be studied. Fibroblast and type II cell proliferation as well as type II cell surfactant related functions will be examined. In addition, alterations in response to growth factors may be mediated through changes in the properties of cell surface receptors, and thus growth factor receptors will be studied both on cells in culture and in situ. Because of differential sensitivity of mature and developing lung to injury, these questions will be examined in both adult and neonatal tissues at specific intervals during the response to injury, determining differences in both the production of and response to factors produced by lung cells in vivo and in vitro. In summary, this proposal seeks to measure the production of specific growth factors by the alveolar macrophage and the type II cell that can influence proliferation and differentiated properties of type II cells and fibroblasts in vivo and in vitro and determine how the production and response to such mediators is altered through developmentally regulated processes and tissue injury. SCOR Project 1 interfaces directly with studies of injury involving regulation of gene expression (SCOR 2), and surfactant behavior (SCOR 4).